Luminacins are novel angiogenesis inhibitors isolated from the fermentation broth of an actinomycete strain designated Streptomyces sp. Mer-VD1207. (Naruse et al. The Journal of Antibiotics, 2000, Vol. 53, No. 6, 579-590). Fourteen active components were isolated, the structures of which are shown below.
 LuminacinComponentR1R2R3R4, R5A1HEtH═OA2HEtH═OB1HiPrH═OB2HiPrH═OC1HEtCHOOMe, HC2HEtCHOOMe, HDHEtCHOH, HE1HiPrCHOOMe, HE2HiPrCHOOMe, HE3HPrCHOOMe, HFCH3EtCHOH, HG1HiPrCHOH, HG2HPrCHOH, HHHEtCOCH3H, H
The luminacin components were tested in a rat aorta tube formation (RATF) model, and were shown to inhibit branching and tube formation without decreasing the number of migrating cells (Wakabayashi et al. The Journal of Antibiotics, 2000, Vol. 53, No. 6, 591-596). This activity was confirmed in another angiogenesis model using human umbilical vein endothelial cells (HUVEC). The inhibitory activities toward tube formation (RATF model and TF model) and endothelial cell proliferation suggest that these compounds are angiogenesis inhibitors. Molecules closely related or identical to C1 and C2 have also been reported to exhibit activities of immunosuppression (Suzuki et al., Kokai Tokkyo Koho, 1983, 116, 686) and low density lipoprotein (LDL) uptake enhancement (Hamaguchi et al., Kokai Tokkyo Koho, 1994, 228, 144). The relationship, if any, of these activities to the angiogenic activity remains to be established.
The newly developing field of angiogenesis inhibitors has vast applications in the treatment of many incurable diseases like cancer. Thus these types of compounds have the potential to significantly impact modern medicine. Accordingly, the demonstrated ability of luminacins to inhibit angiogenesis has generated an interest in further exploring the biological and pharmacological activity of luminacins and analogues thereof. Clearly, there remains a need to develop practical synthetic methodologies to access and examine the therapeutic effect of a variety of novel luminacin analogues, particularly those that are inaccessible by making modifications to the natural product. It would also be of particular interest to develop novel compounds that exhibit a favorable therapeutic profile in vivo (e.g., are safe and effective, while retaining stability in biological media).